Abstract
Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2−/−) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm2) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2−/− macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.
Highlights
Asbestos, a naturally occurring fibrous mineral, predominantly used in construction and shipbuilding, has been associated with neoplastic diseases, such as malignant mesothelioma (MM)and lung cancer [1,2]
The action of LGM2605 in mitigating the effects of asbestos exposure was evaluated by determination of reactive oxygen species (ROS) generation, cytotoxicity and cell death, proinflammatory cytokine secretion, antioxidant enzyme activity, and mRNA levels of Nuclear factor-E2 related factor 2 (Nrf2)-regulated genes
We evaluated the effect of LGM2605 treatment on asbestos-induced intracellular ROS and oxidative stress generation using CellROX® Green Reagent (Figure 1B,C)
Summary
A naturally occurring fibrous mineral, predominantly used in construction and shipbuilding, has been associated with neoplastic diseases, such as malignant mesothelioma (MM)and lung cancer [1,2]. A naturally occurring fibrous mineral, predominantly used in construction and shipbuilding, has been associated with neoplastic diseases, such as malignant mesothelioma (MM). Many studies have been dedicated to the elucidation of the mechanism of how such exposures lead to malignant transformation of the mesothelial cells and, multiple mechanisms have. These are chronic inflammation [6] and generation of reactive oxygen species (ROS) predominantly by activated macrophages which in turn induces signaling pathways resulting in activation of nuclear factor-κB (NF-κB) [7] and the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome [8]. Malignant mesothelioma tumor samples are associated with chronic inflammation, including macrophage infiltration and inflammatory cytokine production [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
